Daily adjunctive therapy with vitamin D 3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Abstract

Objective: Immunotherapy using vitamin D (vitD 3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD 3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). Methods: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD 3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D 3 concentrations. Results: Most subjects had low baseline plasma 25(OH)D 3 levels that increased gradually in the vitD 3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L −1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (−0.52, 95% CI −0.93, −0.10; P = 0.015) while the modified TB score was reduced at week 8 (−0.58, 95% CI −1.02, −0.14; P = 0.01) and 16 (−0.34, 95% CI −0.64, −0.03; P = 0.03). VitD 3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD 3 + PBA group (12.6%). Conclusion: Daily supplementation with vitD 3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.